Since their introduction during the past decade, the newer atypical antipsychotics have been increasingly used for the management with a variety of psychotic disorders and severe behavioral disturbances in older patients, primarily because of their lower risk of extrapyramidal symptoms and tardive dyskinesia compared to conventional neuroleptics. However, in the last few years there has been a growing concern among clinicians and researchers that these medications may present a different set of potentially serious adverse effects, especially long-term Metabolic, Cardiovascular, and Cerebrovascular Effects (MCCE) resulting in weight gain, type 2 diabetes mellitus, hyperlipidemia, and strokes. The goal of the proposed project is to evaluate the risk of MCCE of 4 atypical antipsychotics (aripiprazole, olanzapine, quetiapine, and risperidone), the mediators and moderators of MCCE, and the impact of these side effects on everyday functioning and quality of life in middle-aged and elderly psychiatric patients. This will be a longitudinal, prospective study with serial clinical and laboratory assessments. The strengths of this proposal include its public health importance, use of Equipoise-Stratified randomization (which is scientifically, ethically, and practically superior to the conventional randomization), state-of-the-art clinical and laboratory assessments of MCCE, plans for data sharing that take into account patient's right to confidentiality, an experienced multidisciplinary team of investigators (including experts in metabolic, cardiovascular, and cerebrovascular disorders), and infrastructure support provided by an NIMH-funded Advanced Center for Interventions and Services Research (including its Operations Core, Bioethics Unit, and Methodology, Biostatistics & Data Management Unit) as well as an NIH-supported General Clinical Research Center.